In what may be the biggest blow yet to the world’s largest St. Patrick’s Day parade, the Irish makers of Guinness beer announced Sunday that they’re dropping their sponsorship of Monday’s Manhattan event because of its organizers’ policy banning groups from marching under banners identifying themselves as gay.

“We were hopeful that the policy of exclusion would be reversed for this year’s parade. As this has not come to pass, Guinness has withdrawn its participation. We will continue to work with community leaders to ensure that future parades have an inclusionary policy.”

Guinness beer has long been synonymous with all things Irish, and was targeted by gay-rights activists Sunday, the eve of Monday’s 11 a.m. parade up Fifth Avenue.

The legendary Stonewall Inn gay bar in Greenwich Village announced it would dump barrels of Guinness from its roof in protest of the beer maker’s participation in the parade.

After Guinness, owned by the massive liquor multinational Diageo, announced it would pull out of the parade, the bar called off the protest.

“It’s amazing how the times are changing,” said Carmine Tzavis, a Stonewall bartender. “Thirty years ago, gay people had to hide in fear, and now look what we can accomplish.’’

GLADD President Sarah Kate Ellis issued a statement saying, “Guinness sent a strong message to its customers and employees: Discrimination should never be celebrated.

“As a gay mom who has fond memories of the New York City St. Patrick’s Day Parade, it saddens me that I can’t give those same memories to my own kids because my family isn’t welcome.”

Not everyone agreed with the move.

“Guinness should have just ignored them,” said Ray Brophy, 50, of Ireland, who was knocking back Guinnesses at Connolly’s on West 45th Street. “St. Patrick’s Day isn’t about gay or straight. It’s about celebrating St. Patrick.”

Morris Jones, who was also enjoying a glass of the brew, said, “Guinness has been sponsoring the parade for years and the rules haven’t changed. Changing their tune now just looks foolish.’’

The Ancient Order of Hibernians, which runs the parade, did not return calls for comment.

Guinness made its move after many New York political leaders declined to march unless gay groups are allowed to participate openly. After some 16 years of mayoral involvement in the event, Mayor Bill de Blasio decided to boycott. Most members of the City Council also declined to march in the parade.

Guinness’ move leaves Ford Motors as the only major American corporation that continues to sponsor the New York parade.

Heineken had already dropped its support, saying that the company is “passionate about equality for all people.”

Sam Adams announced that it would drop its sponsorship of Boston’s St. Patrick’s Day Parade, which, like the New York march, bans marchers identifying themselves as gay.

New York City Council Speaker Melissa Mark-Viverito commended the three breweries on Sunday night.

She said they sent “a clear message that New York’s St. Patrick’s Day Parade needs to be inclusive to all New Yorkers.’’